COX-2 inhibition mediated aggregation-induced emission photosensitizer target the Golgi apparatus for selective imaging of cancer cells and enhanced photodynamic therapy
Xiaohan Wang, Xing Wang, Yuanhang Li, Zhengjian Qi
Abstract
Photodynamic therapy (PDT) exerts its therapeutic effects by inducing apoptosis, necrosis, and microvascular damage in tumor cells, but it also causes inflammation and induces the expression of angiogenic factors , accelerating tumor metastasis and proliferation. In this study, aggregation-induced emission (AIE) photosensitizer (PS) for PDT was combined with the cyclooxygenase-2 (COX-2) inhibitor indomethacin (IMC) for cancer-selective imaging and more efficiency in inducing apoptosis in cancer cells. In detail, inhibition of COX-2-mediated AIE PS effectively targeted the Golgi apparatus (GA) of cancer cells to generate large amounts of reactive oxygen species (ROS) in situ, thereby exerting a PDT effect. Specifically, COX-2 and other key enzymes that trigger inflammation and metastasis were significantly inhibited. It had more potent anti-tumor activity (tumor inhibition rate of 64.32 %), as well as anti-metastatic and anti-proliferative effects compared to the use of usual AIE PS.